Novel therapeutic starategy for CEACAM1 expressing colorectal cancer cells beyond the invasion front

表达 CEACAM1 的结直肠癌细胞超越侵袭前沿的新治疗策略

• 批准号: 23591904
• 负责人: YOKOYAMA Shozo
• 金额: $ 2.66万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591904/
• 关键词: CEACAM1; 大腸癌; 癌幹細胞様特性; 抗癌剤感受性; 腺管形成; 癌幹細胞

Enhanced CEACAM-4S (short cytoplasmic isoform) induced CD44 expression, incresed ALDH1 activity, and anchorage indeoendent growth of colorectal cancer cells compared with vector control, suggesting that a possibility that CEACAM1-4S induce CSC property. In clinical setting, Overexpression of CEACAM1-S (short cytoplasmic isoform) at the invasion fronat of colorectal cancer tissue indicated poor survival of patients. By addition of 5FU to colorectal cancer cells on plastic, CEACAM1-4L transfected HT29 cells significantly survived in comparison with CEACAM1-4S or vector control transfected cells. In 3D culture, addition of 5FU induced apoptotic burst of colorectal cancer sphere formed by CEACAM1-4S. A multivariate analysis for recurrence after curative surgery and adjuvant chemotherapy for Stage III colorectal cancer patients showed that the hollow spheroid formation beyond the invasive front is an independent risk factor.

与载体对照相比，增强的CEACAM1-4S诱导CD44表达，ALDH1活性增加，锚定非依赖性生长，提示CEACAM1-4S可能诱导CSC特性。在临床环境中，CEACAM1-S(胞浆短异构体)在结直肠癌组织侵袭前沿的过度表达提示患者的生存不良。与CEACAM1-4S或载体对照细胞相比，CEACAM1-4L转染组HT29细胞在塑料载体上加入5FU后存活时间明显延长。在3D培养中，加入5FU诱导CEACAM1-4S形成的结直肠癌球体发生凋亡。对III期结直肠癌根治性手术和辅助化疗后复发的多因素分析表明，侵袭前线以外的中空椭球形成是一个独立的危险因素。